机构地区:[1]北京市中医药防治重大疾病基础研究重点实验室,中国中医科学院医学实验中心,北京100700 [2]中国中医科学院中药研究所,北京100700
出 处:《中国新药杂志》2022年第22期2262-2269,共8页Chinese Journal of New Drugs
基 金:中国中医科学院科技创新工程(CI2021A00205);中央级公益性科研院所基本科研业务费专项资金(XTCX2021004);国家重点研发计划(2018YFC1708100,2018YFC1708105)。
摘 要:目的:观察生脉饮与多柔比星(doxorubicin, DOX)联合应用对耐DOX乳腺癌小鼠的治疗作用。方法:雌性BALB/c小鼠,随机分为6组,分别为:(1)空白对照组(n=10)。(2)模型组(n=20)。(3) DOX组(n=20)。(4) DOX+生脉饮低剂量组(n=20)。(5) DOX+生脉饮中剂量组(n=20)。(6) DOX+生脉饮高剂量组(n=20)。小鼠乳垫原位接种4T1-Luc/DOX细胞制备耐DOX乳腺癌小鼠模型,动态观察小鼠一般状态及瘤体积;小动物活体成像检测系统分别于造模后2,3,4周对模型小鼠肿瘤生长情况进行动态分析,取材前应用高分辨小动物超声影像系统检测各组小鼠心功能。记录小鼠死亡时间。结果:4T1-Luc/DOX细胞原位接种制备乳腺癌小鼠模型成功率为100%。DOX组及DOX+生脉饮各剂量组在造模2~5周时,小鼠体重低于空白组和模型组。DOX组及DOX+生脉饮中剂量组在造模3周时,肿瘤组织光强值低于模型组。DOX+生脉饮各剂量组3~5周时,瘤体积小于模型组。DOX+生脉饮中、高剂量组在3周时,瘤体积小于DOX组。DOX+生脉饮各剂量组心脏重量低于空白组和模型组。与DOX组比较,DOX+生脉饮中、高剂量组射血分数和短轴缩短率增高。各组死亡率比较:(3)>(5)>(4)>(6)>(2)>(1)。结论:生脉饮与DOX联合应用能够增强DOX治疗乳腺癌效应,减轻DOX引起的心功能损伤,降低肿瘤小鼠的死亡率。Objective: To observe the therapeutic effect of Shengmai Yin combined with doxorubicin(DOX) in mice bearing DOX-resistant breast cancer. Methods: Female BALB/c mice were randomly divided into six groups: control group(group 1, n=10), model group(group 2, n=20), DOX group(group 3, n=10), DOX+Shengmai Yin low dose group(group 4, n=20), DOX+Shengmai Yin middle dose group(group 5, n=20), DOX+Shengmai Yin high dose group(group 6, n=20). Mouse DOX-resistant breast cancer cell line 4 T1_Luc/DOX was injected into mouse mammary fat pad to make the breast cancer model. Mouse status and the tumor volume were dynamically observed. The progression of breast cancer was detected and analyzed by small animal living image system at 2, 3, 4 weeks after modeling. High-resolution small animal ultrasound imaging system was used to test the cardiac function of mice before dissection. The death time of the mice was recorded as well. Results: The successful rate of preparing the mouse breast cancer model by orthotopic implantation of 4 T1-Luc/DOX cells was 100%. Compared with the control and model groups, the body weights in groups 3~6 were decreased at 2~5 weeks after modeling. The light intensity values of tumor in group 3 and 5 were lower than group 2 at 3 weeks after modeling. The tumor volumes of groups 4~6 were smaller than that of the model group at 3~5 weeks after modeling. At 3 weeks after modeling, the tumor volumes in groups 5 and 6 were smaller than that of the DOX group. The heart weights of groups 4~6 were lower than those of the control and model groups. Compared with the DOX group, the left ventricular ejection fraction(LVEF) and fractional shortening(FS) were increased in group 5 and 6. The mortality rate of each group ranged in the following sequence: 3>5>4>6>2>1. Conclusion: The combination of SMY and DOX can improve the therapeutic effect of DOX-resistant breast cancer mice, reduce the myocardial injury induced by DOX, and decrease the mortality.
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